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Review
. 2020 Dec 30;25(4):204-212.
doi: 10.15430/JCP.2020.25.4.204.

Sry-related High Mobility Group Box 17 Functions as a Tumor Suppressor by Antagonizing the Wingless-related Integration Site Pathway

Maha Anani  1 , Ikuo Nobuhisa  2 , Tetsuya Taga  2
Affiliations
Review

Sry-related High Mobility Group Box 17 Functions as a Tumor Suppressor by Antagonizing the Wingless-related Integration Site Pathway

Maha Anani et al. J Cancer Prev. .

Abstract

A transcription factor Sry-related high mobility group box (Sox) 17 is involved in developmental processes including spermatogenesis, cardiovascular system, endoderm formation, and so on. In this article, we firstly review the studies on the relation between the Sox17 expression and tumor malignancy. Although Sox17 positively promotes various tissue development, most of the cancers associated with Sox17 show decreased expression levels of Sox17, and an inverse correlation between Sox17 expression and malignancy is revealed. We briefly discuss the mechanism of such Sox17 down-regulation by focusing on DNA methylation of CpG sites located in the Sox17 gene promoter. Next, we overview the function of Sox17 in the fetal hematopoiesis, particularly in the dorsal aorta in midgestation mouse embryos. The Sox17 expression in hematopoietic stem cell (HSC)-containing intra-aortic hematopoietic cell cluster (IAHCs) is important for the cluster formation with the hematopoietic ability. The sustained expression of Sox17 in adult bone marrow HSCs and the cells in IAHCs of the dorsal aorta indicate abnormalities that are low lymphocyte chimerism and the aberrant proliferation of common myeloid progenitors in transplantation experiments. We then summarize the perspectives of Sox17 research in cancer control.

Keywords: Aotra; Hematopoiesis; Methylation; Neoplasms; Transcription factors.

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Conflict of interest statement

CONFLICTS OF INTEREST No potential conflicts of interest were disclosed.

Figures

Figure 1
Figure 1. Mechanisms underlying the inverse correlation between Sox17 expression and malignancy.
(A) In normal cells, Sox17 protein binds to β-Cat which is an essential factor in the Wnt signaling pathway, and in turn inhibits the transcription activity of the β-Cat/TCF complex which normally induces Wnt-dependent gene expression. (B) In various cancer cells, the expression of Sox17 is downregulated by methylation of its promoter, and the β-Cat/TCF complex induces expression of Wnt-dependent genes. Regulatory factors for increased methylation in the Sox17 gene promoter are not identified. LRP, lipoprotein receptor-related protein; Wnt, Wingless-related integration site; GSK3-β, glycogen synthetase 3β; β-Cat, β-catenin; Sox, Sry-related high mobility group box; TCF, T-cell factor.
Figure 2
Figure 2. Effects of manipulated expression of Sox17 on the hematopoiesis in intra-aortic hematopoietic cell clusters in dorsal aorta at midgestation mouse embryos and adult bone marrow HSPCs.
(A) Sox17-transduced intra-aortic hematopoietic cell clusters maintain the cluster formation with hematopoietic activity and shutdown of the Sox17 expression in Sox17-trausduced clusters results in the dissociation of the cluster and a release of differentiated hematopoietic cells. In transplantation experiments, Sox17-transduced intra-aortic hematopoietic cell clusters have the long-term reconstituting activity with low lymphocyte chimerism, and a greater increase of CMPs. (B) Sox17-transduced HSPCs in adult bone marrow also have the long-term reconstituting activity with low lymphocyte chimerism. Sox, Sry-related high mobility group box; HSPCs, hematopoietic stem/progenitor cells; LT-HSCs, long-term repopulating hematopoietic stem cells; CMP, common myeloid progenitors; HSPCs, hematopoietic stem/progenitor cells.
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